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Biomedical subjects

D O'Neill

Publications and source records attributed to D O'Neill.

At least 73 records · Page 4Linked to original sources
PubMed1997

The possible significance of cytomegaloviral parotitis in infant and early childhood deaths.

OBJECTIVE: To determine whether cytomegaloviral (CMV) parotitis reflects a disseminated disease that increases vulnerability to unexpected death. DESIGN: Necropsy-based cross-sectional study comparing incidences of brain stem microglial nodules and visceral lymphocytic infiltrates in patients with and without CMV parotitis. SUBJECTS: One hundred twelve infants and young children comprising a study group of 40 individuals with CMV parotitis (including 32 whose deaths remained unexplained) and two comparison groups comprising 40 explained and 32 unexplained deaths. MAIN OUTCOME MEASURES: Incidence and variation with age of brain stem microglial nodules and lymphocytic infiltrates in liver and kidneys. RESULTS: Brain stem microglial nodules and lymphocytic infiltrates in liver and kidneys are strongly associated with CMV parotitis; their incidence diminishes with increasing age. CONCLUSIONS: Disseminated disease frequently accompanies CMV parotitis in infants. The resolution of brain stem microglial nodules precedes that of parotitis. Active and previous brain stem involvement may increase vulnerability to unexpected death.

Aging↗
PubMed1996

An element upstream from the human delta-globin-encoding gene specifically enhances beta-globin reporter gene expression in murine erythroleukemia cells.

We have previously shown that a DNA-binding factor specific to adult hematopoietic cells (polypryrimidine-binding factor, PYBF) binds to a pyrimidine-rich region 1 kb upstream from the human delta-globin-encoding gene (HBD). The developmental stage-specificity of PYBF and the location of its binding site between the fetal and adult beta-globin (HBB)-like genes suggest that PBYF and its binding site may function in fetal-to-adult globin gene switching. Here, we describe the effect of 383-bp (delta383) and 99-bp (delta99) sequences containing the PYBF-binding site on transcription from various globin and non-globin promoters, using a transient assay with the cat reporter gene in murine erythroleukemia (MEL) cells, a cell line with abundant PYBF activity. We show that both delta383 and delta99 specifically enhance expression of cat for plasmids containing a human adult globin (HBB) promoter, whereas expression of similar constructs using human fetal (A gamma-) globin (HBG1) or simian virus 40 (SV40) promoters is not enhanced. The results suggest that PYBF and the pyrimidine-rich region upstream from HBD can specifically enhance HBB transcription in adult erythroid cells.

Adult↗
PubMed1996

Expression of a cosmid containing the LCR, (A)gamma, delta, and beta globin genes in mouse erythroleukemia cells.

A novel method involving the packaging of phage particles was used to introduce cosmids containing components of the human beta-globin locus control region (LCR) and the human (A)gamma, delta, and beta globin genes into mouse erythroleukemia (MEL) cells. After stable transfection, MEL clones were selected and analyzed for expression of human genes. Both (A)gamma and beta globin mRNA were expressed in these clones, indicating that MEL cells do not suppress transcription of the human gamma globin gene. The variability of human (A)gamma vs. beta globin expression from clone to clone prevents a clear delineation of differences in the expression of these two genes with a cosmid in which a region potentially involved in gamma-to-beta switching has been deleted. The results suggest that MEL cells are capable of supporting human gamma expression, despite their predominantly adult phenotype.

Adult↗
PubMed1996

Diagnosis of whooping cough: a new era with rapid molecular diagnostics.

A rapid diagnostic procedure, which is based upon the polymerase chain reaction (PCR) genetic amplification technology, was utilized to establish the presence of Bordetella pertussis in nasopharyngeal washes from children. Overall, 14.7% of 456 specimens were positive by either culture or the rapid assay. Culture and PCR were concordant for 62.7% of positive samples; PCR provided an additional increment of 37.3%. PCR-positive, culture-negative specimens were more likely to be found among older patients with more prolonged illness and previous erythromycin therapy (P < 0.01 for all three comparisons). As a single laboratory assay, PCR should be recognized as the current standard for diagnosis.

Bacteriological Techniques↗
PubMed1996

Central dimensions of clinical practice evaluation: efficiency, appropriateness and effectiveness--I.

Successful audit of clinical practice focuses upon the systematic investigation of key aspects of the everyday work of busy clinicians. We contend that the nature and quality of local clinical practice can be characterized by critical examinations of the effectiveness and appropriateness of practice and the efficiency with which effective, appropriate clinical care is delivered to patients. When such a baseline has been established, it becomes possible to compare and contrast characterized local practice with so-called 'evidence-based' practice and agree changes aimed at narrowing the discrepancy between the two. The nature of such changes can be described and their implementation into practice studied, with subsequent quantitative measurement and qualitative description of the resulting benefits to patients. A proper understanding of the concepts of efficiency, appropriateness and effectiveness in clinical care is clearly fundamental to the successful design and applications of methodologies aimed at securing measurable improvements in the quality of patient care. In this first of two articles we examine the concepts of efficiency and appropriateness in clinical practice, with particular emphasis on cost-effectiveness and utilization review. The clinical effectiveness of health care intervention is treated in detail within the second paper, to be published within Volume 2 Number 2 of the Journal of Evaluation in Clinical Practice (Miles et al. 1996f).

Clinical Medicine↗
PubMed1996

Central dimensions of clinical practice evaluation: efficiency, appropriateness and effectiveness--II.

That a treatment selected for a given condition works, or that it works better than alternative treatments, or that it was selected because it works as well as but is cheaper than alternative treatments, should be of pivotal concern to clinicians and is of central concern to patients and to health care managers. Attempts to address these concerns have resulted in what is now widely termed the 'effectiveness movement'. The protagonists of the movement have been concerned to create a culture of evaluation and inquiry within which the formulation of evidence-based clinical guidelines and their introduction into routine practice have played a prominent part. The need to ensure cost effectiveness of clinical intervention has been at least as emphasized as the need to ensure the clinical effectiveness of health care interventions. Although cost-effectiveness analyses are now an indispensable feature of practice guideline formulation and treatment evaluation, few studies have examined any deterioration in patient outcome associated with successful cost containment. An adequate understanding of the concept of clinical effectiveness and the associated aims of the 'effectiveness movement' is central to an understanding of the future nature and extent of health service provision, not simply in the UK but also internationally. Having examined the concepts of efficiency and appropriateness previously (O'Neill, Miles & Polychronis 1996, Journal of Evaluation in Clinical Practice 2, 13-27) we move in this second of two articles to a detailed explanation of the concept of effectiveness, and to an examination of the derivation and use of clinical practice guideline, concluding with a consideration of the role of practice guidelines in ensuring the cost effectiveness of health care intervention. The reservation is expressed that a 'guidelines culture', when established, will be manipulated by health care commissioners for largely political purposes, creating a systematic bias in the purchasing process that will actively disadvantage a range of patient groups.

Cost-Benefit Analysis↗
PubMed1996

Syncope: driving advice is frequently overlooked.

Consecutive referrals to a syncope clinic were asked about the frequency of enquiries about driving status by referring general practitioners and/or hospital specialists. Although 40% were drivers, only 13% of patients had been previously asked about driving, and 12% of drivers had experienced symptoms whilst driving. This represents an important oversight on the part of referring doctors.

Adult↗
PubMed1995

Nuclear factor binding sites in human beta globin IVS2.

The second intron of the human beta globin gene (beta IVS2) has been previously identified as a region required for proper expression of beta globin. To further characterize this region, we have footprinted the entire beta IVS2 and have analyzed regions of interest by electrophoretic mobility shift assay. Through these studies we have identified four utilized binding sites for the erythroid regulatory factor GATA-1, two sites bound by general transcription factor Oct-1, two sites bound by the nuclear matrix attachment DNA binding protein special A-T-rich binding protein 1, and a site bound by a potential homeobox protein. Additionally, we have found several factors displaying temporal or tissue specificity by electrophoretic mobility shift assay, which may be potentially involved in the regulation of beta globin expression. These proteins are not supershifted by antibodies to factors important in erythroid regulation such as GATA-1, NFE-2, or YY1, or by antibodies against more general transcription factors.

Animals↗
PubMed1995

Dissolution of intracardiac mass lesions in the primary antiphospholipid antibody syndrome.

The antiphospholipid antibody syndrome has numerous cardiac manifestations, including valvular thickening, insufficiency, and mass lesions. The mass lesions may be confused with atrial myxomas and other vegetations, sometimes necessitating a surgical diagnosis. There are no prospective studies on treatment or follow-up of intracardiac lesions in antiphospholipid antibody syndrome. We prospectively followed up three patients with antiphospholipid antibody syndrome for intracardiac lesions (one atrial and two mitral valve masses) complicated by systemic embolization. Anticoagulation led to complete resolution of the masses in 6 weeks to 3 months. We propose that initial treatment of an intracardiac lesion in patients with antiphospholipid antibody syndrome should be a trial of systemic anticoagulation before surgical intervention.

Adult↗
PubMed1995

Occupational disorders affecting agricultural workers in tropical developing countries: results of a literature review.

This paper presents the results of a literature review undertaken to determine the nature and extent of occupational health problems in tropical agriculture and to identify opportunities for ergonomics intervention. Occupational disorders were categorized as follows: disorders associated with the use of pesticides; disorders associated with biomechanical and postural demands; and disorders associated with harmful materials other than pesticides. It was concluded that the high rate of pesticide poisoning in tropical agriculture is partly a consequence of the inappropriate transfer of technology from industrialized to developing countries. Ergonomics intervention has the potential to reduce the incidence of occupational pesticide poisoning in developing countries. Biomechanical disorders are commonly presumed to be prevalent in tropical agriculture, but the evidence to confirm this is lacking. Again, ergonomics intervention has the potential to minimize such disorders, but the cultural significance associated with traditional tools and practices must be considered in such a development programme. Disorders associated with contact with harmful materials have been described as occupational diseases. Pesticides aside, these have received little attention, partly because it is difficult to distinguish between occupational and non-occupational incidences of such diseases. Opportunities to reduce the occurrence of these occupational diseases could be limited.

Journal Article↗
PubMed1995

Extracapsular cataract surgery with and without intraocular lens implantation in Fuchs heterochromic cyclitis.

PURPOSE: To compare the surgical and postoperative complications and visual outcome of extracapsular cataract extraction (ECCE) with and without intraocular lens (IOL) implant in Fuchs heterochromic cyclitis. METHODS: The records of 77 patients with Fuchs heterochromic cyclitis who had undergone ECCE were reviewed. Of a total of 77 eyes, a posterior chamber IOL (PC IOL) was implanted in 43 eyes, whereas 34 eyes did not receive an implant. RESULTS: In the pseudophakic group, 40 (93%) eyes achieved 20/40 or better. This level also was achieved in 29 (85%) eyes not receiving an implant. Intraoperative anterior chamber hemorrhage was documented in 18 eyes but there was no correlation with preoperative gonioscopic findings. A temporary or permanent elevation of intraocular pressure was noted in five of eight eyes that had marked anterior chamber hemorrhage. Severe postoperative uveitis occurred in ten eyes and was more common in patients with glaucoma who had PC IOL implantation, but this did not adversely affect the visual outcome. Of 40 eyes with PC IOL implant, severe postoperative uveitis developed in 7. In six of these seven eyes, the implant was a three-piece lens with polypropylene haptics. Severe postoperative uveitis developed in 6 of 16 eyes with preoperative glaucoma. Five of these six eyes had a PC IOL implant. Of the 34 aphakic patients, 10 (29%) were intolerant of contact lens correction. There was no difference in the incidence of postoperative uveitis, cystoid macular edema, and development of glaucoma between the two groups. CONCLUSION: Implantation of PC IOLs in ECCE in patients with Fuchs heterochromic cyclitis appears to a safe procedure, but careful postoperative follow-up of intraocular pressure, particularly in patients with intraoperative hemorrhage or postoperative uveitis, is indicated.

Adolescent↗
PubMed1995

Variability in scoring the Hachinski Ischaemic Score.

Multi-infarct dementia (MID) may be the second most common form of dementia in later life. A commonly used aid in the clinical diagnosis of MID is the Hachinski Ischaemic Score (HIS). The usefulness of this score is controversial, and we hypothesized that this is because many items of the HIS are open to a wide range of interpretations. We therefore canvassed 45 research and academic centres in the United Kingdom and Ireland with an interest in dementia to assess the variability of interpretation of the HIS. Five template cases were constructed, in which were embedded items which were felt to be potentially contentious. Fifty-five out of 94 (59%) respondents replied. There was a very wide variation in the scores assigned to each vignette. In only five of 65 items was there complete agreement among replies: in general there was a very large range for each item. Thirty of the items showed less than 90% agreement. The apparent simplicity of the HIS conceals possibilities for ambiguous interpretation of individual items. This is a property common to many 'simple' rating scales. It should not lead to outright rejection of these scales, but rather to a refinement and clarification of the scoring and assessment techniques.

Activities of Daily Living↗
PubMed1995

Appropriateness of hospital use in the United Kingdom: a review of activity in the field.

OBJECTIVE: This paper reviews experience, in both research and application, with measures of appropriateness applied to the utilization of hospital inpatient services in the UK. BACKGROUND: The evolution of different methods for measuring appropriateness of use and the associated reasons for misutilization are described. RESEARCH AND APPLICATION: Recent research developments and applications are outlined and discussed. CONCLUSION: Contemporary enthusiasm with "Diagnosis Independent Explicit Criteria Utilization Review Instruments" is observed and some of the underlying influences are explored.

Health Services Research↗